The lifelong maintenance of mesencephalic dopaminergic neurons by Nurr1 and engrailed

Specific vulnerability and degeneration of the dopaminergic neurons in the substantia nigra pars compacta of the midbrain is the pathological hallmark of Parkinson’s disease. A number of transcription factors regulate the birth and development of this set of neurons and some remain constitutively expressed throughout life. These maintenance transcription factors are closely associated with essential neurophysiological functions and are required ultimately for the long-term survival of the midbrain dopaminergic neurons. The current review describes the role of two such factors, Nurr1 and engrailed, in differentiation, maturation, and in normal physiological functions including acquisition of neurotransmitter identity. The review will also elucidate the relationship of these factors with life, vulnerability, degeneration and death of mesencephalic dopaminergic neurons in the context of Parkinson’s disease

Persistent postoperative pain and healthcare costs associated with instrumented and non-instrumented spinal surgery: a case-control study

Purpose: To compare rates of persistent postoperative pain (PPP) after lumbar spine surgery—commonly known as Failed Back Surgery Syndrome—and healthcare costs for instrumented lumbar spinal fusion versus decompression/discectomy. Methods: The UK population-based healthcare data from the Hospital Episode Statistics (HES) database from NHS Digital and the Clinical Practice Research Datalink (CPRD) were queried to identify patients with PPP following lumbar spinal surgery. Rates of PPP were calculated by type of surgery (instrumented and non-instrumented). Total healthcare costs associated with the surgery and covering the 24-month period after index hospital discharge were estimated using standard methods for classifying health care encounters into major categories of health care resource utilization (i.e., inpatient hospital stays, outpatient clinic visits, accident and emergency attendances, primary care encounters, and medications prescribed in primary care) and applying the appropriate unit costs (expressed in 2013 GBP). Results: Increasing the complexity of surgery with instrumentation was not associated with an increased rate of PPP. However, 2-year healthcare costs following discharge after surgery are significantly higher among patients who underwent instrumented surgery compared with decompression/discectomy. Conclusions: Although there is a not insubstantial risk of ongoing pain following spine surgery, with 1-in-5 patients experiencing PPP within 2 years of surgery, the underlying indications for surgical modality and related choice of surgical procedure do not, by itself, appear to be a driving factor

The incidence and healthcare costs of persistent post-operative pain following lumbar spine surgery in the United Kingdom: a cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) : a cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES)

OBJECTIVE: To characterise incidence and healthcare costs associated with persistent postoperative pain (PPP) following lumbar surgery. DESIGN: Retrospective, population-based cohort study. SETTING: Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. PARTICIPANTS: Population-based cohort of 10 216 adults who underwent lumbar surgery in England from 1997/1998 through 2011/2012 and had at least 1 year of presurgery data and 2 years of postoperative follow-up data in the linked CPRD-HES. PRIMARY AND SECONDARY OUTCOMES MEASURES: Incidence and total healthcare costs over 2, 5 and 10 years attributable to persistent PPP following initial lumbar surgery. RESULTS: The rate of individuals undergoing lumbar surgery in the CPRD-HES linked data doubled over the 15-year study period, fiscal years 1997/1998 to 2011/2012, from 2.5 to 4.9 per 10 000 adults. Over the most recent 5-year period (2007/2008 to 2011/2012), on average 20.8% (95% CI 19.7% to 21.9%) of lumbar surgery patients met criteria for PPP. Rates of healthcare usage were significantly higher for patients with PPP across all types of care. Over 2 years following initial spine surgery, the mean cost difference between patients with and without PPP was £5383 (95% CI £4872 to £5916). Over 5 and 10 years following initial spine surgery, the mean cost difference between patients with and without PPP increased to £10 195 (95% CI £8726 to £11 669) and £14 318 (95% CI £8386 to £19 771), respectively. Extrapolated to the UK population, we estimate that nearly 5000 adults experience PPP after spine surgery annually, with each new cohort costing the UK National Health Service in excess of £70 million over the first 10 years alone. CONCLUSIONS: Persistent pain affects more than one-in-five lumbar surgery patients and accounts for substantial long-term healthcare costs. There is a need for formal, evidence-based guidelines for a coherent, coordinated management strategy for patients with continuing pain after lumbar surgery

Beat synchronization across the lifespan: intersection of development and musical experience

Rhythmic entrainment, or beat synchronization, provides an opportunity to understand how multiple systems operate together to integrate sensory-motor information. Also, synchronization is an essential component of musical performance that may be enhanced through musical training. Investigations of rhythmic entrainment have revealed a developmental trajectory across the lifespan, showing synchronization improves with age and musical experience. Here, we explore the development and maintenance of synchronization in childhood through older adulthood in a large cohort of participants (N = 145), and also ask how it may be altered by musical experience. We employed a uniform assessment of beat synchronization for all participants and compared performance developmentally and between individuals with and without musical experience. We show that the ability to consistently tap along to a beat improves with age into adulthood, yet in older adulthood tapping performance becomes more variable. Also, from childhood into young adulthood, individuals are able to tap increasingly close to the beat (i.e., asynchronies decline with age), however, this trend reverses from younger into older adulthood. There is a positive association between proportion of life spent playing music and tapping performance, which suggests a link between musical experience and auditory-motor integration. These results are broadly consistent with previous investigations into the development of beat synchronization across the lifespan, and thus complement existing studies and present new insights offered by a different, large cross-sectional sample

Faster maturation of selective attention in musically trained children and adolescents : Converging behavioral and event-related potential evidence

Previous work suggests that musical training in childhood is associated with enhanced executive functions. However, it is unknown whether this advantage extends to selective attention-another central aspect of executive control. We recorded a well-established event-related potential (ERP) marker of distraction, the P3a, during an audio-visual task to investigate the maturation of selective attention in musically trained children and adolescents aged 10-17 years and a control group of untrained peers. The task required categorization of visual stimuli, while a sequence of standard sounds and distracting novel sounds were presented in the background. The music group outperformed the control group in the categorization task and the younger children in the music group showed a smaller P3a to the distracting novel sounds than their peers in the control group. Also, a negative response elicited by the novel sounds in the N1/MMN time range (similar to 150-200 ms) was smaller in the music group. These results indicate that the music group was less easily distracted by the task-irrelevant sound stimulation and gated the neural processing of the novel sounds more efficiently than the control group. Furthermore, we replicated our previous finding that, relative to the control group, the musically trained children and adolescents performed faster in standardized tests for inhibition and set shifting. These results provide novel converging behavioral and electrophysiological evidence from a cross-modal paradigm for accelerated maturation of selective attention in musically trained children and adolescents and corroborate the association between musical training and enhanced inhibition and set shifting.Peer reviewe

Infantile myofibromatosis: a nontraumatic cause of neonatal brachial plexus palsy

Most injuries to the neonatal brachial plexus occur acutely at birth, and are iatrogenic in origin. However, when weakness is accompanied by atrophy, nontraumatic etiologies should be considered. The differential diagnosis of chronic congenital brachial plexopathy includes cervical bone malformations, humeral osteomyelitis, varicella, and compression from various types of infantile tumors. An illustrative male infant delivered at 37 weeks of gestation with wasted musculature of the left upper arm, ipsilateral Horner's syndrome, and a hemidiaphragm is presented. On further examination, this patient manifested an underlying cervical tumor compressing the brachial plexus. Diagnostic steps leading to the pathologic identification of a solitary cervical myofibroma included physical examination, electromyography, radiographic imaging, and open biopsy. This report emphasizes the importance of differentiating acute from chronic congenital plexus palsy and of recognizing the possibility that infection or neoplasm may underlie the latter

Reoperation following lumbar spinal surgery: costs and outcomes in a UK population cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES)

Purpose: To assess the likelihood of persistent postoperative pain (PPP) following reoperation after lumbar surgery and to estimate associated healthcare costs. Methods: This is a retrospective cohort study using two linked UK databases: Hospital Episode Statistics and UK Clinical Practice Research Datalink. Costs and outcomes associated with reoperation were evaluated over a 2-year postoperative period using multivariate logistic regression for cases who underwent reoperation and controls who did not, based on demographics, index surgery type, smoking status, and pre-index comorbidities using propensity score matching. Results: Risk factors associated with reoperation included younger age and the presence of diabetes with complications or rheumatic disease. The rate of PPP after reoperation was much higher than after index surgery, with 79 of 200 (39.5%; 95% CI 32.5%, 46.5%) participants experiencing ongoing pain compared with 983 of 5022 (19.5%; 95% CI 18.5%, 20.7%) after index surgery. Mean costs in the 2 years following reoperation were £1889 higher (95% CI £2, £3809) than for patients with PPP who did not undergo repeat surgery over an equivalent follow-up period. With the cost of reoperation itself included, the mean cost difference for patients who underwent reoperation compared with matched controls rose to £7221 (95% CI £5273, £9206). Conclusions: High rates of PPP and associated healthcare costs suggest that returning to the operating room is a complex and challenging decision. Spinal surgeons should review whether the potential benefits of additional surgery are justified when other approaches to managing and relieving chronic pain have demonstrated superior outcomes

Decrease in gamma-band activity tracks sequence learning

Learning novel sequences constitutes an example of declarative memory formation, involving conscious recall of temporal events. Performance in sequence learning tasks improves with repetition and involves forming temporal associations over scales of seconds to minutes. To further understand the neural circuits underlying declarative sequence learning over trials, we tracked changes in intracranial field potentials (IFPs) recorded from 1142 electrodes implanted throughout temporal and frontal cortical areas in 14 human subjects, while they learned the temporal-order of multiple sequences of images over trials through repeated recall. We observed an increase in power in the gamma frequency band (30–100 Hz) in the recall phase, particularly in areas within the temporal lobe including the parahippocampal gyrus. The degree of this gamma power enhancement decreased over trials with improved sequence recall. Modulation of gamma power was directly correlated with the improvement in recall performance. When presenting new sequences, gamma power was reset to high values and decreased again after learning. These observations suggest that signals in the gamma frequency band may play a more prominent role during the early steps of the learning process rather than during the maintenance of memory traces